Abstract
Metastasis and drug resistance are major barriers for the treatment of non-small cell lung cancer (NSCLC). To explore new therapeutic options, we successfully encapsulated MicroRNA-34a (miR-34a), a potent endogenous tumor suppressor in NSCLC into S6 aptamer-conjugated dendrimer to form lung cancer-targeted gene delivery nanoparticles (PAM-Ap/pMiR-34a NPs). PAM-Ap/pMiR-34a NPs had a diameter of 100–200 nm and Zeta potential of ~30 mV at applied N/P ratio. The aptamer conjugation significantly improved cellular uptake as well as gene transfection efficiency of PAM-Ap/pMiR-34a NPs in cultured NSCLC cells. We showed that PAM-Ap/pMiR-34a NPs enhanced the regulation of targeted genes, BCL-2 and p53 in vitro. In addition, we revealed PAM-Ap/pMiR-34a NPs significantly inhibited cell growth, migration, invasion and induced apoptosis of lung cancer cells compared with non-targeted NPs. The method provided a novel therapeutic strategy for the experimental treatment of NSCLC.
Highlights
Lung cancer is the leading cause of cancer-related death around the world [1]
We developed PAMAM-PEG-aptamer connection (PAM-Ap) using S6, an aptamer selected against A549 lung cancer cells by cell-SELEX [23] and adopted to functionalize PAMAM G5.0, we mixed the PAM-Ap with pMiR-34a to construct PAM-Ap/pMiR-34a nanoparticles (PAM-Ap/pMiR-34a NPs) to deliver of pDNA to lung cancer cells
Fetal bovine serum (FBS), RPMI-1640 culture medium, Dulbecco's phosphate-buffered saline (DPBS), trypsin, penicillin-streptomycin and YOYO-1 iodide were purchased from Invitrogen/Life Technologies (Carlsbad, CA)
Summary
Lung cancer is the leading cause of cancer-related death around the world [1]. 85% of all the clinical lung cancer cases are non-small cell lung cancer (NSCLC) [2, 3]. Despite numerous advances in surgical treatment, chemotherapy and molecular targeted agents for NSCLC, metastasis and multidrug resistance are still major causes for failures in treating lung cancer patients [4, 5]. It is highly desirable to develop new therapeutic approaches beyond conventional treatment for NSCLC. MicroRNAs (miRNAs) have been shown to play an important role in the progress of human cancers and can be effective targets for cancer therapy [6]. MiRNAs are small RNAs of ~22 nucleotide long that are critical regulators of gene
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